Mohammed, who has claimed involvement in numerous attacks and is representing himself, is expected to challenge the ability of the judge, Army Colonel Stephen Henley, to objectively preside over the case.
Two of his co-defendants are also representing themselves during the hearings.
Unusually, the Guantanamo military tribunal system allows defendants to challenge the judge in a process known as "voir dire".
Defence lawyers are also expected to request that the case is dismissed over concerns that Brigadier General Thomas Hartmann, a military commissions legal adviser, exerted unlawful influence over prosecution teams.
"General Hartmann became the lead prosecutor when his role was supposed to be the neutral adviser," said Army Major Jon Jackson, a military defence lawyer for Mustafa al-Hawsawi, a Saudi defendant.
Clive Stafford-Smith, who has represented some of the prisoners at Guantanamo, told Al Jazeera on Monday that it was "extraordinarily unlikely" there will be justice for the detainees.
"The whole process in Guantanamo is a mockery of justice. Just last week a military prosecutor was going public in the media about how unfair the process is. It's not me as defence lawyer saying this; it's the prosecutors themselves," he said.
Five relatives were selected to observe the trial after the Pentagon organised a lottery system from a pool of more than 100.
A friend or relative will accompany each of the family members.
Relatives will sit in a viewing gallery at the back of the courtroom, separated from the proceedings by an acrylic glass wall and an audio time-delay.
The time-delay will enable security officials to cut transmission of the proceedings, which are expected to last for one week, if sensitive material considered to be classified is mentioned.
Barak Obama, the US president-elect, has announced that he will close the Guantanamo camp once in office.